Institute of Pharmaceutical and Medicinal Chemistry

Germany

Institute of Pharmaceutical and Medicinal Chemistry

Germany
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Heimes K.,Institute of Pharmaceutical and Medicinal Chemistry | Hauk F.,Institute of Pharmaceutical and Medicinal Chemistry | Verspohl E.J.,Institute of Pharmaceutical and Medicinal Chemistry
Phytotherapy Research | Year: 2011

Peppermint oil (Mentha à - piperita L. (Lamiaceae) has been shown to exert potent antiemetic properties, but its mode of action has not yet been elucidated. Among its active constituents (-)-menthol is the most important. Three different in vitro models were used to investigate the effects on 5-HT 3 receptors (serotonin receptor subtype): [ 14C] guanidinium influx into N1E-115 cells which express 5-HT 3 receptors, isotonic contractions of the isolated rat ileum and equilibrium competition binding studies using a radioactively labelled 5-HT 3 receptor antagonist ([ 3H]GR65630) (3-(5-methyl-1H-imidazol-4-yl)-1-(1-methyl- 1H-indol-3-yl)-1-propanone). Both peppermint oil and (-)-menthol inhibited [ 14C]guanidinium influx through 5-HT 3 receptor channels as well as contractions of the ileum induced by serotonin. Neither the peppermint oil nor (-)-menthol, however, was able to displace [ 3H]GR65630 from 5-HT 3 binding sites. It may be concluded that peppermint oil and (-)-menthol exert their antiemetic effect at least partly by acting on the 5-HT 3 receptor ion-channel complex, probably by binding to a modulatory site distinct from the serotonin binding site. © 2010 John Wiley & Sons, Ltd.


Gonnissen D.,University of Munster | Qu Y.,University of Munster | Qu Y.,CAS National Center for Nanoscience and Technology | Langer K.,University of Munster | And 8 more authors.
International Journal of Nanomedicine | Year: 2016

Within the last years, progress has been made in the knowledge of the properties of medically used nanoparticles and their toxic effects, but still, little is known about their influence on cellular processes of immune cells. The aim of our comparative study was to present the influence of two different nanoparticle types on subcellular processes of primary monocytes and the leukemic monocyte cell line MM6. We used core-shell starch-coated superparamagnetic iron oxide nanoparticles (SPIONs) and matrix poly(lactic-co-glycolic acid) (PLGA) nanoparticles for our experiments. In addition to typical biocompatibility testing like the detection of necrosis or secretion of interleukins (ILs), we investigated the impact of these nanoparticles on the actin cytoskeleton and the two voltage-gated potassium channels Kv1.3 and Kv7.1. Induction of necrosis was not seen for PLGA nanoparticles and SPIONs in primary monocytes and MM6 cells. Likewise, no alteration in secretion of IL-1β and IL-10 was detected under the same experimental conditions. In contrast, IL-6 secretion was exclusively downregulated in primary monocytes after contact with both nanoparticles. Two-electrode voltage clamp experiments revealed that both nanoparticles reduce currents of the aforementioned potassium channels. The two nanoparticles differed significantly in their impact on the actin cytoskeleton, demonstrated via atomic force microscopy elasticity measurement and phalloidin staining. While SPIONs led to the disruption of the respective cytoskeleton, PLGA did not show any influence in both experimental setups. The difference in the effects on ion channels and the actin cytoskeleton suggests that nanoparticles affect these subcellular components via different pathways. Our data indicate that the alteration of the cytoskeleton and the effect on ion channels are new parameters that describe the influence of nanoparticles on cells. The results are highly relevant for medical application and further evaluation of nanomaterial biosafety. © 2016 Gonnissen et al.


PubMed | CAS National Center for Nanoscience and Technology, chemicell GmbH, Heart Genetics, University of Munster and Institute of Pharmaceutical and Medicinal Chemistry
Type: | Journal: International journal of nanomedicine | Year: 2016

Within the last years, progress has been made in the knowledge of the properties of medically used nanoparticles and their toxic effects, but still, little is known about their influence on cellular processes of immune cells. The aim of our comparative study was to present the influence of two different nanoparticle types on subcellular processes of primary monocytes and the leukemic monocyte cell line MM6. We used core-shell starch-coated superparamagnetic iron oxide nanoparticles (SPIONs) and matrix poly(lactic-co-glycolic acid) (PLGA) nanoparticles for our experiments. In addition to typical biocompatibility testing like the detection of necrosis or secretion of interleukins (ILs), we investigated the impact of these nanoparticles on the actin cytoskeleton and the two voltage-gated potassium channels Kv1.3 and Kv7.1. Induction of necrosis was not seen for PLGA nanoparticles and SPIONs in primary monocytes and MM6 cells. Likewise, no alteration in secretion of IL-1 and IL-10 was detected under the same experimental conditions. In contrast, IL-6 secretion was exclusively downregulated in primary monocytes after contact with both nanoparticles. Two-electrode voltage clamp experiments revealed that both nanoparticles reduce currents of the aforementioned potassium channels. The two nanoparticles differed significantly in their impact on the actin cytoskeleton, demonstrated via atomic force microscopy elasticity measurement and phalloidin staining. While SPIONs led to the disruption of the respective cytoskeleton, PLGA did not show any influence in both experimental setups. The difference in the effects on ion channels and the actin cytoskeleton suggests that nanoparticles affect these subcellular components via different pathways. Our data indicate that the alteration of the cytoskeleton and the effect on ion channels are new parameters that describe the influence of nanoparticles on cells. The results are highly relevant for medical application and further evaluation of nanomaterial biosafety.


PubMed | Institute of Pharmaceutical and Medicinal Chemistry
Type: Journal Article | Journal: Phytotherapy research : PTR | Year: 2011

Peppermint oil (Mentha piperita L. (Lamiaceae) has been shown to exert potent antiemetic properties, but its mode of action has not yet been elucidated. Among its active constituents (-)-menthol is the most important. Three different in vitro models were used to investigate the effects on 5-HT(3) receptors (serotonin receptor subtype): [(14)C]guanidinium influx into N1E-115 cells which express 5-HT(3) receptors, isotonic contractions of the isolated rat ileum and equilibrium competition binding studies using a radioactively labelled 5-HT(3) receptor antagonist ([(3)H]GR65630) (3-(5-methyl-1H-imidazol-4-yl)-1-(1-methyl-1H-indol-3-yl)-1-propanone). Both peppermint oil and (-)-menthol inhibited [(14)C]guanidinium influx through 5-HT(3) receptor channels as well as contractions of the ileum induced by serotonin. Neither the peppermint oil nor (-)-menthol, however, was able to displace [(3)H]GR65630 from 5-HT(3) binding sites. It may be concluded that peppermint oil and (-)-menthol exert their antiemetic effect at least partly by acting on the 5-HT(3) receptor ion-channel complex, probably by binding to a modulatory site distinct from the serotonin binding site.

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